The present invention relates to a clay based catalytic process for the preparation of acylated aromatic ethers. More particularly, the present invention relates to the catalyzed acylation of anisole (methoxybenzene) and veratrole (1,2- dimethoxybenzene) for the preparation of acylated aromatic ether, namely, p-methoxyacetophenone and 3,4-dimethoxyacetophenone respectively, using a series of lantanide cation exchanged clay based catalysts.
Acylated aromatic ethers are of commercial importance in fine chemicals industries, as many synthetic fragrances and pharmaceuticals contains an acyl group, and these ethers are useful intermediates. Acylated anisole is used for synthesis of 2-(4-Methoxybenzoyl) benzoic acid, the sodium salt of which is used as sweetening agent. Similarly, acylated veratrole is a synthon for preparation of vesnarinone 1-(3,4-Dimethoxybenzoyl)-4(1,2,3,4-tetrahydro-2-oxo-6-quinolinyl) piperazine which is a cardiotonic drug.
Reference is made to U.S. Pat. No. 62747441 B1 (Aug. 14, 2001, B. M. Choudary et al.) wherein it is disclosed that acylation of heteroaromtic compounds like furan, thiophene, or pyrrole with the anhydride of C2-5 carboxylic acid (e.g. acetic anhydride) was carried out using Fe+3 exchanged Montmorillonite clay. The reaction was carried out in the temperature range of 0 to 130xc2x0 C. for 1 to 24 hours and the 2-acylaromatic compound was separated by conventional methods to obtain 2-acetylpyrrole of high purity. The drawback of this process is the longer reaction time and high temperature.
Reference is made to the work of B. M. Choudary et al, Applied Catalysis A, General 171 (1998) 155-160 which describes the acylation of aromatic ethers with acid anhydrides in the presence of cation exchanged clays viz., Fe+3 and Zn+2 exchanged montmorillonite clays. The reaction mixture of 46 millimoles of anisole and 10 millimoles of acetic anhydride and 250 mg of catalysts was stirred under nitrogen atmosphere. After 10 hours it gives conversion in the range of 25 to 70 percent. The drawback of this process is long reaction time, and the catalyst shows loss in activity. Reference is made to U.S. Pat. No. 5,637,773 (1993: Jean-Roger Desmurs et al.) wherein it is disclosed that 40 millimoles of an aromatic substrates and 10 millimoles of acylating agents with excess amount of Bismuth halide as a catalyst, was mixed at room temperature and then refluxed the reaction mixture for 6 hours to gives 67% of 4-acylated anisole. The drawback of this process is that more than stochiometric amounts of bismuth chloride was used and also poses problem of post-reaction catalysts separation. Furthermore, the Lewis acid must be eliminated from the reaction medium by carrying out acidic or basic hydrolysis at the end of the reaction.
Reference is made to German Patent DE 3809260 (1989, Botta A., et al.) wherein anisole and acetic anhydride were stirred for 3 hours with Mordenite zeolite catalysts at 160xc2x0 C. under 20 bar of nitrogen pressure to give 75% conversion with 98% selectivity for p-methoxyacetophenone. This process has disadvantage of operating at high temperature and very high pressure and also needs a solvent for uniform mixing. Reference is made to Japanese Patent 1993-317557 (19931217. C. A.124;8397 Myata, Akira et al.) wherein a mixture of veratrole and propionyl chloride, in the presence of Zeolite-xcex2 was refluxed for three hours to give ca, 70% of 3,4-dimethoxypropiophenone. The drawback of the process is that it uses propionyl chloride as an acylating agent, which generates toxic hydrochloric acid during acylation reaction
Reference is made to the work of C. Kuroda et al, (Sei. Papers Inst. Phys. Chem. Res. 18, pp 51-60 (1932)) which describes the preparation of methoxyacetophenones by the reaction of an aromatic compound carrying methoxy group with acetyl chloride in the presence of excess amount of AlCl3 to obtain high conversions. This process has disadvantages like more than stochiometric amounts of aluminum chloride due to complexation with the ketone formed and also involved process of post reaction effluent treatment and use of corrosive and irritant AlCl3. The major drawback of the above stated process is separation of catalysts after completion of the reaction. This necessitates a long, expensive treatment following hydrolysis, extraction of the organic phase, separation of organic and aqueous phase and even drying of latter. Further, there are problems with aqueous saline effluent which has to be neutralized and which necessities additional operation. The Lewis acid cannot be recycled, as it has been hydrolyzed.
Reference is made to the work of H. Burton and P. F. G. Praill (Journal of Chemical Society, April-1950, pp-1203-1206) wherein it is reported that Acetyl perchlorate formed in-situ from silver perchlorates and acetyl chloride, is an effective acylating agent and will convert anisole into p-methoxyacetophenone in about 70% yield. However, this process has disadvantages of using perchlorates which is hazardous chemical. Reference is made to the work of E. J, Bourne, et al. (Journal of Chemical Society, March-1951, pp-718-720) wherein trifluoroacetic anhydride catalyst is shown to promote, the condensation between suitably activated aromatic compound and carboxylic acid or sulphonic acid to give ketones or sulphones, respectively. In this process, reaction was done at room temperature. Anisole was added to a mixture of trifluroacetic anhydride and acetic acid. After three hours the solution was poured into the excess of sodium hydrogen carbonate solution and then extracted by chloroform The extract were dried, filtered and evaporated to dry syrup. After crystallization it gave 78% of p-methoxyacetophenone.
The reported process is multi-step process wherein separation of the product with very high recovery is a limitation.
Reference is made to the work of Cullinane N. M. et al. (Journal of Chemical Society, Feb-952, pp-376-380) wherein acylation of benzene, toluene and anisole is reported using TiCl4 as a catalyst. Acids, acid chlorides and anhydrides were used as the acylating agents. Acid is reported to be the least and anhydride the most effective towards the formation of acylated products. With anisole (0.15 g-mols) and acetic anhydride (0.1 g-mol) and titanium tetrachloride (0.22 g-mol), the yield of p-acylated product was reported 76% after 4 hours. With anisole (0.2 g-mols) and benzoic acid (0.2 g-mols) and titanium tetrachloride (0.4 g-mols) the yield of p-acylated product was 63% after 1.5 hours. The process has disadvantage of separation of product, as it requires more than one step, like hydrolysis, separation of organic layer and finally removal of solvent at reduced pressure.
The main object of the present invention is to provide clay based catalytic process for the preparation of acylated aromatic ethers, which obviates the drawbacks as detailed above.
Another object of the invention is to develop clay based acylation process for aromatic ethers, which operates at moderate conditions of pressure, temperature and without the requirement of any solvent and yields high conversions for veratrole and for anisole.
Another object of the invention is to provide a process using solid acid heterogeneous catalysts, which are environmentally friendly, safe in handling and the acylating agent does not generate any hazardous byproduct.
Another object of the invention is to provide a process wherein acylation of aromatic ether occurs selectively at para position.
Another object of the invention is to provide a process where acylation of aromatic ether is carried out catalytically with high atom efficiency without giving rise to byproducts.
Accordingly the present invention provides a process for the preparation of an acylated aromatic ether which comprises acylating the aromatic ether with an acylating agent in presence of a solid acid heterogeneous catalyst comprising a rare earth cation exchanged clay based catalyst, separating the catalyst and the acylated aromatic ether obtained.
In one embodiment of the invention, the lanthanide cation exchanged clay catalyst is an upgraded smectite clay wherein the hydrogen ion is exchanged with a sodium ion.
In another embodiment of the invention, the hydrogen ion is exchanged with a sodium ion using an acid selected from the group consisting of HCl, HNO3, and an organic acid.
In another embodiment of the invention, the rare earth ion is selected from the group consisting of lanthanum, cerium, neodymium, praseodymium and samarium.
In a further embodiment of the invention, the amount of rare earth ion in the catalyst is in the range of 5 to 10 weight % of the clay.
In a further embodiment of the invention, the rare earth ion is obtained using a soluble salt of the rare earth selected from the group consisting of nitrate, chloride and acetate.
In another embodiment of the invention, the acylation of the aromatic ether is carried out in a single step under solvent free condition and at a temperature in the range of 80 to 120xc2x0 C. and under atmospheric conditions without generating any by-product.
In a further embodiment of the invention, the acylation of the aromatic ether is carried out at a temperature of 100xc2x0 C.
In another embodiment of the invention, the acylating agent is selected from the group consisting of a chloride and a carboxylic acid anhydride.
In another embodiment of the invention, the carboxylic acid anhydride is acetic acid anhydride or a homologue thereof.
In another embodiment of the invention, the catalyst is separated and recycled.
In another embodiment of the invention, the aromatic ether is selected from the group consisting of veratrole and anisole.
In another embodiment of the invention the process is solvent free with the aromatic ether itself acting as the solvent.
In yet another embodiment of the invention the catalytic reaction is carried Out in the range from 1 to 20 atmospheres.
In yet another embodiment of the present invention the ether to catalyst ratio is in the range of 1.3 to 1:5.
The invention also relates to a clay based catalytic process for the preparation of an acylated aromatic ether which comprises (i) preparing upgraded smectite clay in the range of 0.5 to 5% weight percent; (ii) drying the clay in the temperature of 80 to 120xc2x0 C. for 8 to 12 hours; (iii) exchanging hydrogen ion for sodium ion using a mineral acid selected from the group consisting of HCl and HNO3 or an organic acid; (iv) preparing Lanthanide exchanged clay using a soluble salt of a lanthanide cation; (v) maintaining the ether to catalyst ratio in the range of 1 to 5; mixing the catalyst so prepared with the aromatic ether and an acylating agent and acylating the aromatic ether at a reaction temperature in the range of 80 to 120xc2x0 C. and time in the range of 1 to 9 hours under solvent free reaction mixture at atmospheric pressure; (vi) separating the catalyst and the acylated product by distillation.
In a typical procedure for the preparation of a clay based catalysts, the raw clay is upgraded by sedimentation to remove quartz, grits etc impurities. Wet solid clay is separated from the clay slurry by ultracentrifuge and naturally dried from 6 to 12 hours, followed by drying at 80xc2x0 C. to 120xc2x0 C. for 4 to 8 hours. Thus dried clay was treated with acid solution to convert the clay into H-form 10 gm of the clay thus prepared H-form of clay was refluxed with 100 ml of 0.01 M solution of soluble salt like nitrate, chloride or acetate of relative lanthanide cations for 6 hours. Then catalysts was filtered washed with hot distilled water till the filtrate became anion free and dried overnight 110xc2x0 C. for removing the moistures, clay was activated at 120xc2x0 C. for 4-6 hrs before using for reactions. A typical chemical analysis of clay used for making catalysts was.
The clays prepared were characterized for crystallinity by using X-ray powder diffraction using Philips X""perts MPD model and for BET surface area using Micromeritics ASAP-surface area analyzers.
Catalytic studies using above catalysts were done in continuous stirred tank reactor (CSTR) of 50 ml capacity having temperature controller, water circulator, magnetic stirrer and moisture trap. Typically, 5.5 g of veratrole (or 4.3 g of anisole) and 3.5 g of acetic anhydride were taken in a 50 ml capacity round bottom flask to which 2 gm of the catalyst after activation at 120xc2x0 C. for 4 to 10 hours in muffle furnace was added. The round bottom flask was fitted with a condenser through which constant temperature water was circulated. Moisture trap was attached at the end of the condenser. The contents of the flask were constantly stirred using a magnetic stirrer. The flask was kept in an oil bath whose temperature was slowly raised to desired reaction temperature. The contents of the flask were analyzed by gas chromatography at different time intervals ranging from 1 to 8 hours. The yield was followed over time by taking aliquots which were analyzed by Gas Chromatography HP model 6890 using capillary column HP-5. Percent yield of p-acyl anisole or p-acyl veratrole was calculated using following equation
Percent Yield=number of moles of para acyl aromatic ether actually formed/number of moles of para acyl aromatic ether theoretically expected,
In the present invention upgraded clay was exchanged with soluble salt of lanthanide cations like lanthanum cerium, neodymium, praseodymium, samarium ranging from 5 to 10 wt % of the clay to make them more active towards acylation of anisole and veratrole. Further this improved catalytic process obviates the need of any solvent and the reaction can be carried out at atmospheric pressure. The lanthanide cations in the interlayer space of clays helps the catalytic conversion to be carried out at moderate temperature.
The inventive steps adopted in this invention are: (i) Clays are modified with rare earth in the range of 5 to 10 weight % to make the catalysts more compatible with acylation reactions; (ii) the acylation reaction is carried out in single step so that the multi-step process can be avoided; (iii) the lower temperature and pressure favors the selectivity for para position, which is desired; (iv) the catalytic reaction proceeds at relatively moderate temperature of 100xc2x0 C. and at atmospheric pressure, which obviates the need of high temperature and pressure, (v) acylation occurs without use of any solvent and without using hazardous and effluent generating acylating agent.